Curr. Opin. Chem. Biol. 2019, 52, 93-101
Nucleic acid-based enzymes have recently joined their proteinaceous counterparts as important biocatalysts. While RNA enzymes (ribozymes) are found in nature, deoxyribozymes or DNAzymes are man-made entities. Numerous ribozymes and DNAzymes have been identified by Darwinian selection methods to catalyze a broad array of chemical transformations. Despite these important advances, practical applications involving nucleic acid enzymes are often plagued by relatively poor pharmacokinetic properties and cellular uptake, rapid degradation by nucleases and/or by the limited chemical arsenal carried by natural DNA and RNA. In this review, the two main chemical approaches for the modification of nucleic acid-based catalysts, particularly DNAzymes, are described. These methods aim at improving the functional properties of nucleic acid enzymes by mitigating some of these shortcomings. In this context, recent developments in the post-SELEX processing of existing nucleic acid catalysts as well as efforts for the selection of DNAzymes and ribozymes with modified nucleoside triphosphates are summarized.